Autonomous Filter Element

ABSTRACT

An autonomous filter device and a method for improving the filter life and performance is disclosed. The filter element is equipped with one or more sensors, adapted to measure one or more characteristics. In response to the measured characteristic, the control logic within the filter element is able to determine an appropriate response. For example, the control logic may determine that a sudden, but temporary, blockage has occurred in the filter membrane. In response, the control logic may initiate a specific response designed to alleviate the blockage. The control logic will then determine the success of the response, based monitoring any change in the fluid characteristics. Based thereon, the control logic may alert the operator that the filter element must be replaced. Alternatively, if the response was successful in correcting the blockage, the control logic need not notify the operator, as the filter element is back to normal operating operation.

This application is a divisional of U.S. Ser. No. 12/699,996 filed Feb.4, 2010, which claims priority of U.S. Provisional Patent ApplicationSer. No. 61/152,329, filed Feb. 13, 2009 and U.S. Provisional PatentApplication Ser. No.61/241,053, filed Sep. 10, 2009, the disclosures ofwhich are incorporated by reference in their entireties.

BACKGROUND OF THE INVENTION

Filters are used in a multitude of applications, from removing crystalsfrom wine, to removing impurities from drinking water and motor oil, toremoving particulates from bioreactors, fermentors or other chemicalprocesses.

Filters in each of these applications have issues associated with theiruse. In some cases, the issues may be specific to a particularapplication. For example, a number of containers, including but notlimited to pharmaceutical containers, such as bioreactors and buffertanks, require the ability to vent the internal gasses to the outsideenvironment, or to take in fresh gas from outside the container. To doso and maintain sterility, it is common to include a sterile vent filteron the container. In some instances, excess gases, such as carbondioxide or steam, produced during the reaction must be released from thecontainer. In other instances, sparge or charge gasses, such as oxygenor air are intentionally added into the container.

One specific issue with these vent filters is maintaining an acceptablegas flow. A common problem is that the materials, typically water vapor,within the container can be subject to condensation since in mostapplications, gas temperature during operation is greater than ambient(i.e. 35° C. typical for a bioreactor and 80° C. for a WFI tank). Ifthis material condenses on the vent filter, it will restrict the flow ofgasses between the container and the outside environment by blocking thepores of the filter thereby reducing its effective surface area for gastransport.

Additionally, the natural foaming that occurs from biomanufacturingprocesses can accumulate on the filter and restrict air conduction. Thefoam is typically controlled in one of several ways. First, anti-foamingagent can be added to the container so that the surface tension isreduced and foam is not created. Alternatively, the container or filterhousing may be designed to break bubble formation before it moves up tothe filter membrane. Both of these approaches add complexity to thedesign of the vent filter and reaction process.

To counteract these phenomena, vent filters are typically made fromhydrophobic membranes, which resist condensation within the filter porestructure. However, despite the use of hydrophobic membranes, it isknown that condensation or plugging may still occur on the vent filterelement. One possible solution to this problem is the use of externalheating elements, which serve to elevate the temperature of the filterelement, thereby reducing the condensation on the element.

These external heating elements are typically applied after the filterhas been assembled, and can suffer from several failure modes. In someinstances, the temperature sensor on the external heating element canfail, causing the filter to overheat, potentially compromising itsintegrity. In other instances, the sensor failure may lead to aninactive heater, which does not perform the desired function. In otherinstances, the heating element is only able to monitor the heat of thestainless steel housing around the filter element. Thus, changes in gasflow through the filter, which affect the filter's temperature, cannotbe measured or detected by the external heating element. This can resultin a lack of sufficient heat, or an overabundance, depending on the flowrate of the fluid in the filter.

Additionally, in large containers, the vent filter may be physicallyremote from the operator, such as on a different level of the building,and therefore, cannot be easily inspected by the operator. Thus, issuesof integrity or flow rate may be ongoing for a period of time beforethey are detected using current implementations.

Other filter applications may have other unique issues. For example,tangential flow filters (TFF filters) may become clogged by the proteinwhich it is filtering. Maintaining proper backpressure can helpalleviate this problem.

In addition to application specific issues, there are issues that aregeneric for all filters. For example, the issue of integrity is commonto all applications. A small breach in the filter membrane causesparticulate to pass through the filter. Such a breach may becatastrophic depending on the application. For example, if the filter isused to insure a sterile interface or boundary, such a breach isunacceptable.

A second generic issue is that of reduced flow rate due to an excessiveamount of particulate trapped against the filter membrane. This issuecauses many filter vendors to suggest that filters be changed at regularintervals. For example, automotive oil filters should be changed atintervals determined by elapsed time or elapsed mileage. Similarly,water filters for refrigerators may have a life cycle measured in monthsof use or gallons of water filtered.

Today, most filters have two modes of operating. The first mode isnormal operating mode. In this mode, the filter is operating normally,removing particulate as intended. In many embodiments, this is thedefault operation of the filter, and nothing is required to ensure thatthe filter remains in this mode. However, in some applications, it maybe necessary to perform additional maintenance actions to insure thatthe filter remains in operating mode. For example, it may be necessaryto heat the filter element to insure that the fluid being filteredremains in a particular state (such as liquid or gas), as describedabove in relation to the vent filter.

The second mode of operation also common to all filters is end of life.In this mode, the filter has exceeded its useful life. Such an event mayoccur due to an excessive buildup of particulate on the filter membrane.Typically, the ability of the filter element to pass fluid at anacceptable flow rate is compromised. In extreme cases, the fluid flow iscompletely stopped. Another failure that leads to end of life is anintegrity breach. If the filter element is no longer integral, it cannotperform its function, and therefore has reached its end of life. Filtersmust be replaced upon reaching their end of life.

Although filters typically are only used in these two modes, there maybe advantageous to have a third mode of operation, known as recoverymode. In this mode, the filter is not performing optimally, however, ithas not actually reached its end of life. The performance may havedegraded by a process condition outside the typical operating, such aswhen a large particulate blocks the membrane, or a large number ofparticulates arrive simultaneously. The filter membrane itself is notclogged yet, however, a large or unexpected amount of particulate hascompromised the filter's ability to operate efficiently. In the case ofthe vent filter, this may occur accidently in a bioreactor when spargegas surges spraying the protein foam on the filter membrane. In mostfilter applications, this mode is indistinguishable from end of life,and therefore is remedied in a similar fashion, typically by replacementof the filter.

An improved device and method that can more reliably monitor, detect andcontrol these three modes of operation would be beneficial. Such adevice and method can reduce cost, by maximizing the useful life of thefilter element, and by minimizing the downtime associated with a filterreplacement.

SUMMARY OF THE INVENTION

The problems of the prior art are overcome by the present invention,which discloses an autonomous filter device and a method for improvingthe filter life and performance. The filter element is equipped with oneor more sensors, adapted to measure one or more characteristics orparameters of the fluid, such as temperature, pressure, or flow rate. Inresponse to the measured characteristic or parameter, the control logicwithin the filter element is able to determine an appropriate response.For example, the control logic may determine that a sudden, buttemporary, blockage has occurred in the filter membrane. In response tothis, the control logic may initiate a specific response designed toalleviate the blockage. This response may be a temperature change, avibration, a change in fluid flow path, or some other action. Thecontrol logic will then determine the success of the response, based onmonitoring any change in the fluid characteristics. Based thereon, thecontrol logic may alert the operator that the filter element must bereplaced. Alternatively, if the response was successful in correctingthe blockage, the control logic need not notify the operator, as thefilter element is back to normal operating operation. In otherembodiments, the control logic also regulates the operating mode of thefilter, such as by insuring that the fluid passing there through is at apredetermined temperature or pressure.

In other embodiments, the filter element works in conjunction with thesurrounding support mechanism to provide the required functionality. Forexample, in certain embodiments, the filter may determine thatparticulates have reduced the flow rate. In response thereto, the filtermay communicate to the associated support mechanism, which may alter thefluid flow through the filter.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a flowchart of the present invention;

FIG. 2 illustrates a representative schematic of the present invention;

FIG. 3 illustrates a container having a vent filter;

FIG. 4 illustrates a vent filter of the present invention with anintegrated heating element;

FIG. 2 illustrates a representative schematic of one embodiment of thepresent invention;

FIG. 6 shows a phase diagram;

FIG. 7 illustrates a representative flowchart that can be used by theprocessing unit during normal operating mode in one embodiment of thepresent invention;

FIG. 8 illustrates the operation of a plurality of flow sensors in afiltering element;

FIGS. 9 a-9 d show flow rate graph for various filter elements;

FIG. 10 illustrates a filter in accordance with a second embodiment ofthe present invention;

FIG. 11 illustrates flow paths through various filter types;

FIG. 12 shows the flow path of a tangential flow filter (TFF) ;

FIG. 13 shows a second embodiment of the flow path of a TFF filter;

FIG. 14 shows the forces acting upon a TFF filter;

and

FIG. 15 illustrates a TFF filter in accordance with an embodiment of thepresent invention.

DETAILED DESCRIPTION OF THE INVENTION

As described above, a filter element preferably has three modes ofoperation. These three modes are illustrated in FIG. 1. The operatingmode 10 is used during the majority of the filter's life. In most cases,no actions are required to insure that the filter remains in operatingmode. However, in some embodiments, a maintenance action 12 may beperformed, either continuous or periodically, to insure that the filterremains operational. Such an action may be a thermal cycle, vibration,pressure or fluid backflow or other remedial action.

After some amount of use, a measured parameter or characteristic of thefilter, such as the flow rate of the filtered fluid, upstream and/ordownstream pressure, or fluid temperature, may deviate from theacceptable ranges. If this event 27 occurs after an extended period oftime, or as predicted by the manufacturer, the filter may simply havereached its end of life. In such a case, the mode of the filter changesfrom operating mode 10 to end of life mode 30, by way of natural wearoutpath 27.

Alternatively, the parameter may change suddenly, indicating that thefilter has an integrity issue, and is no longer acting to filterparticulate. Such an event also changes the mode of the filter fromoperating mode 10 to end of life 30 via path 27.

However, at times, a degradation event 15 may occur unexpectedly orinstantaneously. In such a scenario, the event causes the filter toperform suboptimally, as may be determined by an abrupt change is one ofthe measured parameters or characteristics. A sudden change in themeasured parameter would be inconsistent with typical wear out, andtherefore may indicate an abnormal, perhaps temporary blockage hasoccurred. For example, a dramatic decrease in fluid flow rate mayindicate that the filter has instantaneously become blocked. In such ascenario, the filter may move from operating mode 10 to recovery mode20.

In recovery mode 20, the filter attempts to correct the blockage byactuating one or more corrective or remedial procedures. Theseprocedures may include increasing temperature, changing fluidcirculation paths, shaking the filter membrane, changing or reversingtransmembrane pressure and others. This corrective action may beperformed one time, and if the corrective action is successful inrestoring the measured parameter or characteristic to an acceptablevalue, the filter transitions back to operating mode 100, via path 18.

In some embodiments, the corrective action may be performed a pluralityof times, as shown in path 13. If after a predetermined number ofcorrective action attempts, the parameter has not returned to anacceptable value, the filter then transitions to end of life 30, viapath 25.

Having defined a generic flowchart that demonstrates the modes of thefilter of the present invention, a generic diagram of the structure ofthe filter will be described.

FIG. 2 shows a representative schematic of the filter element 100 of thepresent invention. This filter element 100 contains control logic 140 toallow it to understand and transition between the modes described above.To provide this level of intelligence, a power supply must be provided.In certain embodiments, a battery or an electrical outlet is used tosupply the required energy for the heating element. However, in otherembodiments, the filter is self-contained and receives power wirelessly.In certain embodiments, a magnetic induction power coupling loop 110 isused in conjunction with a magnetic field to generate the required powersource. In this way, the filter is not tethered to an external powersupply, nor is there an active power source resident in the filter.Methods for attaching and integrating a magnetic field are described inco-pending application Ser. No. 12/079,396, which is hereby incorporatedby reference.

In one embodiment, the magnetic induction power coupling loop 110 isused to create a voltage which is used by the sensors, actuators and byany associated circuitry within the filter. Any voltage variationsneeded to operate the filter element are performed by circuitry withinthe vent filter. In another embodiment, the magnetic field is modifiedso as to vary the voltage received by the power coupling loop 110.

In some embodiments, one or more sensors 120,121,122 are used to monitorat least one parameter or characteristic of the filter element. Couplingloop 110 is used to create an induced voltage from the external field.This voltage, which is an AC voltage 112, is then rectified and smoothedusing a rectifier circuit 113 to create a DC voltage 115. This DCvoltage 115 is then used to power any active circuitry, such as tuners,sensors, CPUs and the like.

A sensor 120 is used to monitor a parameter or characteristic of thefilter element and relay this information back to a processing unit 140,such as a central processing unit (CPU). The processing unit 140includes a storage device, such as a semiconductor memory, which is usedto store instructions for the CPU and store various parameters andsettings. The sensor 120 may be wired, or wireless, depending on itslocation within the filter. For example, if the sensor 120 is located inthe housing near the control circuit, a wired or wireless configurationmay be used. If however, the sensor 120 is located away from the controlcircuit, it may be advantageous to use a wireless sensor.

In one embodiment, the wireless sensor 120 is embedded in the end cap ofthe filter element 100. In other embodiments, the sensor 120 is affixedto, or embedded in, the filter element 100 at a different point, such ason the downstream side of the filter core element. In some applications,the temperature of the filter element may exceed 145° C., therefore asensor capable of withstanding this temperature should be employed.Similarly, the temperature within the container 100 may cycle from lowertemperatures to higher temperatures and back, therefore the sensorshould be capable of withstanding this temperature cycling.

In one embodiment, a wireless transmitter is also located near, orintegrated with, the sensor 120. In the preferred embodiment, thewireless transmitter and the sensor 120 are encapsulated in a singleintegrated component. Alternatively, the transmitter and the sensor 120can be separated, and in communication with each other, such as viaelectrical signals. Various types of wireless communication devices arepossible, including RFID, Zigbee, 802.11a/b/g, and other protocols.

The processor unit 140 compares the value measured by the sensor 120 tothe desired or accepted value, or range of values, of the parameter orcharacteristic. The value returned by the sensor 120 may be an analogvalue, such as one proportional to the parameter measured, or may be adigital signal. Based on the value returned, the processor 140determines whether the filter is still in operating mode, or whether itshould transition to a different mode.

As shown in FIG. 1, in some embodiments, a maintenance action 12 can betaken to enable the filter to remain in operating mode 10. This actionmay take many forms, including but not limited to temperature orbackpressure modification. In these embodiments, the processing unit 140controls actuator 150, which performs the required maintenance action.

If the measured parameter or characteristic, as seen by sensor 120,deviates from an accepted value or range, the CPU 140 may transition torecovery mode 20. In this mode, the filter actuates a corrective action13, using actuator 160. This actuator may be the same actuator as theactuator used to implement the corrective action 13, or may be adifferent actuator. Suitable actions that may be employed includetemperature or backpressure modification, circulation path modification,filter vibration, or other similar actions.

After the CPU has controlled actuator 160, it again checks the measuredvalue returned by sensor 120. If the value has returned to a normalrange, the CPU terminates the corrective action 13 and returns tooperating mode 10. If the measured value is still unacceptable, the CPU140 may opt to repeat the corrective action 13 one or more times. If themeasured value returns to an acceptable range during this time, the CPU140 returns to normal mode 10. If, however, the value remainsunacceptable, the CPU 140 transitions to the end of life state 30.

In some embodiments, the filter 100 may employ more than one sensor 120.For example, the filter may have a temperature sensor 120, an upstreampressure sensor 121 and a downstream pressure sensor 122. In otherembodiments, a different combination of sensors may be used. In theseembodiments, the CPU 140 can use measured values from one or more of thesensors in determining what mode to enter and to determine theappropriate action. For example, the CPU 140 may use the output ofseveral sensors (e.g. temperature and pressure) to control themaintenance action 12. However, it may use a single sensor (e.g. flowrate) to determine whether the corrective action was successful.

In some embodiments, an indicator 170 is used to alert the operator thatthe filter has reached end of life 30. This indicator 170 may be visual,auditory, tactile or some other means. Upon reaching end of life 30, theCPU 140 may actuate indicator 170.

In some embodiments, the actuator 150 and/or actuator 160 may not bephysically located within the filter element 100. For example, inapplications where changes in pressure or changes in circulation pathare employed, the CPU 140 may control valves or other devices which arephysically separate from the filter. This control can be via wired orwireless communication.

The state diagram and structure described above can be used in a numberof different applications. Several of these applications will bediscussed below. However, this list is not exhaustive and those ofordinary skill in the art will appreciate that other applications canalso utilizes the teachings disclosed herein.

EXAMPLE 1 Vent Filter

In a first embodiment, a vent filter is employed. In a first embodiment,the filter is used as a vent filter.

FIG. 3 shows a container having such a vent. Typically, the container201 is constructed from rigid materials, such as stainless steel andrigid plastic. In other embodiments, the container may be a flexibleplastic material. To allow gasses to pass between the inside of thecontainer 201 and the outside environment, typically a vent filter 200is used. In the embodiment shown in FIG. 3, the filter element 200 islocated at the top surface of the container 201, so that it is separatedfrom the material contained within the container 201.

Vent filtration systems are used not only for bioreactors, but also forgrowth media, buffer solution, WFI (Water For Injection) preparationsystems and filling applications. These vent filters are sterilizedusing a suitable technique, such as autoclave, Steam-In-Place, gassterilization, such as using ETO (ethylene oxide) gas, or gammairradiation.

Vent filters are typically installed in one of two configurations. Inthe embodiment shown in FIG. 3, a replaceable cartridge is installedwithin a stainless steel housing, and the entire assembly is affixed tothe container. One such filter is an AERVENT® filter available fromMillipore Corporation of Billerica, Mass. A second common configurationis the use of a self-contained plastic capsule with its own plastichousing. One such filter is an OPTICAP® capsule filter with an AERVENThydrophobic membrane available from Millipore Corporation of Billerica,Mass.

FIG. 4 shows a vent filter having an integrated heating element. Thevent filter 200 may be of any suitable type, such as but not limited toa disposable filter capsule or a replaceable filter cartridge. Ventfilters typically have an outer porous plastic housing or sleeve 210, amembrane 220 and an inner core 230. The housing 210 and the inner core230 are porous, preferably with a series of large openings (212 and 232respectively) to allow fluid to move from the exterior of the filterthrough the housing 210 via its openings 212 through the membrane 220and the openings of the porous core 230 to an outlet (not shown) whichis connected to the core 230 and the base 240. A heating element islocated within the vent filter 200, such as integrated into the plastichousing 210 or the inner core 230. In some embodiments, the membrane 220is surrounded by a support layer (not shown). This support layer may bea more rigid porous membrane, a nonwoven or a mesh grid. In someembodiments, the heating element is placed in the support layer. Thevent filter has a base 240, which attaches to the container. The ventfilter 200 also has a closed top end 250.

FIG. 5 shows a representative schematic of the vent filter. In itssimplest form, the heating elements 330 include a conductive wire, whichis electrically isolated from its surrounding, connected to a powersupply. The passage of current through the wire serves to heat the wire,thereby elevating the temperature of the surroundings. Modifications inthe current passed through the wire serve to provide a mechanism tocontrol the temperature. Thus, higher temperatures are achieved bypassing more current through the wire. Alternatively, the current canremain fixed, while the duty cycle during which it is applied is varied.In other embodiments, a combination of current amount and time durationis used to regulate the temperature of the filter.

Further heating elements may be in the form of grids or meshes or porousmats that are electrically conductive and capable of generating thedesired heating effect. They may be made of metal or other conductivematerials such as carbon, graphite or carbon nanotubes.

To affect a change in temperature, a power supply must be provided. Incertain embodiments, a battery or an electrical outlet is used to supplythe required energy for the heating element. However, in otherembodiments, the vent filter is self-contained and receives powerwirelessly. In certain embodiments, a magnetic induction power couplingloop is used in conjunction with a magnetic field to generate therequired power source. In this way, the vent filter is not tethered toan external power supply, nor is there an active power source residentin the filter. Methods for attaching and integrating a magnetic fieldare described in co-pending application Ser. No. 12/079,396, which ishereby incorporated by reference.

In one embodiment, the magnetic induction power coupling loop is used tocreate a voltage which is used by the heating element and by anyassociated circuitry within the filter. Any voltage variations needed tochange the temperature of the heating element are performed by circuitrywithin the vent filter. In another embodiment, the magnetic field ismodified so as to vary the voltage received by the power coupling loop.

In some embodiments, one or more temperature sensors are used to controland monitor the temperature of the heating element and its surrounds.FIG. 5 shows a representative schematic of the circuitry required for anactively controlled vent filter. Coupling loop 310 is used to create aninduced voltage from the external field. This voltage, which is an ACvoltage 312, is then rectified and smoothed using a rectifier circuit313 to create a DC voltage 315. This DC voltage 315 is then used topower any active circuitry, such as tuners, sensors, CPUs and the like.

A temperature sensor 320 is used to monitor the temperature of theheating element 330 and relay this information back to a processing unit340, such as a central processing unit (CPU). The temperature sensor maybe wired, or wireless, depending on its location within the vent filter.For example, if the sensor is located in the housing near the controlcircuit, a wired or wireless configuration may be used. If however, thetemperature sensor is located away from the control circuit, it may beadvantageous to use a wireless sensor.

Suitable sensors include a thermistor, which is a resistor with a hightemperature coefficient of resistance, and a transducer, which is anintegrated circuit. The sensor can also be of another type, including,but not limited to, a diode, a RTD (resistance temperature detector) ora thermocouple.

In one embodiment, the wireless temperature sensor 320 is embedded inthe end cap of the filter element 300. In other embodiments, thetemperature sensor is affixed to, or embedded in, the filter element ata different point, preferably on the downstream side. In someapplications, the temperature of the filter element may exceed 145° C.,therefore a sensor capable of monitoring this temperature should beemployed. Similarly, the temperature within the container 100 may cyclefrom lower temperatures to higher temperatures and back, therefore thetemperature sensor should have a response time sufficient to be able tomeasure temperature cycling.

In one embodiment, a wireless transmitter is also located near, orintegrated with, the temperature sensor 320. In the preferredembodiment, the wireless transmitter and the temperature sensor 320 areencapsulated in a single integrated component. Alternatively, thetransmitter and the sensor 320 can be separated, and in communicationwith each other, such as via electrical signals. Various types ofwireless communication devices are possible, including RFID, Zigbee,802.11a/b/g, and other protocols.

The processor unit 340 then compares the temperature value measured bythe temperature sensor to the desired temperature and adjusts thecurrent through the heating element 330 accordingly. The value returnedby the temperature sensor may be an analog value, such as oneproportional to the temperature detected, or may be a digital signal.The method used by the processing unit to make this adjustment can beany suitable means, including but not limited to PID control,proportional control or any other method.

The processing unit 340 varies the current through the use of currentcontrol circuit 350. This circuit 350 controls the amount of currentpassing through the heating element 330, using conventional means. Insome embodiments, the control circuit 350 varies the duty cycle of thecurrent passing through heating element 330. In other embodiments, thecircuit 350 varies the magnitude of the current passing through theheating element 330.

In some embodiments, a second temperature sensor 360 is used as a faulttolerant device, such as a thermal relay or switch, to insure that thevent filter does not overheat in the case of a failure of the firstsensor 320.

Preferably these temperature sensors are placed in proximity to theheating element 330 so as to accurately report the temperature of thefilter elements.

In another embodiment, the circuitry within the vent filter is verysimplistic, comprising only of a wireless temperature sensor and aninduction coil. In this embodiment, the control of the voltage isperformed external to the filter and the magnetic field is adjusted tochange the current through the heating element. This embodiment requiresless electronics within the filter, but requires additional externallogic and control.

As described above, external heaters simply supply a constant amount ofheat to the filter elements, as they cannot detect the internalconditions of the filter. In one embodiment, the heating circuit of FIG.3 is utilized with an intelligent processing unit. For example, apressure sensor 370 may be added to the filter element, adapted tomeasure the pressure within the container.

As was described with respect to the temperature sensor, the pressuresensor may be wired or wireless. This sensor 370 is capable ofgenerating an output, which varies as a function of the pressure of thesurrounding environment. In another embodiment, the sensor 370 is adifferential sensor, whereby its output is a function of the differenceis pressure between two areas. This output can be in the form of ananalog voltage or current, or can be a digital value or pulse. In thepreferred embodiment, the output varies linearly with the pressure,however this is not a requirement. Any output having a knownrelationship, such as logarithmic or exponential, to the surroundingpressure, can be employed. In such a situation, a transformation of theoutput can be performed to determine the actual measured pressure.

In some applications, the temperature of the filter element may exceed145° C., therefore a sensor that is stable at these temperatures shouldbe employed. Similarly, a transmitter capable of withstanding thistemperature should be employed. Finally, the temperature with thecontainer 100 may cycle from lower temperatures to higher temperaturesand back, therefore the pressure sensor should be able to withstandtemperature cycling.

There are multiple embodiments of this pressure sensor 370. For example,this sensor can be constructed using micro-electro-mechanical system(MEMS) technology, a piezoelectric element, a conductive or resistivepolymer, including elastomers and inks, or a transducer. These examplesare intended to be illustrative of some of the types of sensors that canbe used; this is not intended to be an exhaustive list of all suchsuitable pressure sensors. Additionally, these sensors can be made usingSilicon on Insulator (SOI) technology, as described in copendingapplication Ser. No. 12/502,259.

In addition, an alert mechanism 380 may be in communication with theprocessing unit 340. This enables the filter element to alert theoperator that it has determined that the filter has reached its end oflife and is in need to replacement.

This filter can be used in the manner described in FIG. 1. In operatingmode, the vent filter must insure that the fluid being filtered remainsin gas phase. Figure shows a traditional phase diagram. By monitoringtemperature and/or pressure, the CPU in the vent can determine phasethat the fluid is in. By varying the current being passed through theheating elements, the CPU can insure this gaseous phase is maintained.

Thus, in this embodiment, there is a maintenance action 12 (as shown inFIG. 1).

FIG. 7 shows a representative flowchart of the control loop required toregulate the current flowing through the heating element duringoperating mode. First, the processing unit queries the pressure sensorto determine the pressure within the container, as shown in Box 500. Theprocessing unit then queries the temperature sensor to determine thetemperature within the container, as shown in Box 510. The processingunit then compares this set of values to the phase diagram for the givenmaterial. In some embodiments, an equation is stored within the storageelement of the processing unit which represents the gas/liquid line 400.In other embodiments, a set of points whose coordinates correspond tothe gas/liquid line 400 are stored in the storage element of theprocessing unit. The processing unit compares the actual readings tothose stored in the storage element. Based on this comparison, theprocessing unit can determine whether the operating conditions are suchthat the material is in its gaseous state. If not, the processing unitincreases the current in the heating element to raise the temperature,as shown in Box 540. In a further embodiment, if the material is in itsgaseous state, the processing unit compares the values to the gas/liquidline 400. If the values produce a point that is close to the line 400,then a proper amount of heat is being used to maintain the environment,as shown in Box 570. However, if the point is far from the line 400,this implies that the temperature may be reduced without fear ofcondensation. In this case, the current in the heating element isreduced, as shown in Box 560.

The flowchart of FIG. 7 is executed repeatedly, so as to maintain theheating element at a proper temperature. The adjustments to the currentmay be based on any control algorithm. For example, a proportionalalgorithm, a P-I algorithm (proportional-integral), a P-D(proportional-derivative) or a P-I-D algorithm(proportional-integral-derivative) algorithm may be used to determinethe current adjustment. Other algorithms are also known and within thescope of the invention.

The CPU continues executing this flowchart as long as the measuredparameters stay within acceptable ranges. The filter begins in operatingmode 10. By reading the pressure sensor 370 and the temperature sensor320, the processing unit can determine the phase that the potentiallyclogging material is in, as shown in FIG. 6. The goal of the controlsystem is to insure that the material remains in gaseous form. Thus, itcontinuously monitors the pressure and temperature within the container,and adjusts the current being passed through the heating elements toinsure that this condition is met.

The use of such an algorithm allows flexibility in the placement of thecontainer. In other words, the present system can adapt to differentoperating conditions (cold, warm or hot temperatures), and heat thefilter accordingly and efficiently.

In a further embodiment, flow rate detectors are incorporated in thevent filter. FIG. 8 illustrates a filter 600, where the flow of materialis indicated by the arrows. The fluid enters the core 610, passesthrough the membrane 620 and exits to the exterior of the filter. Insome embodiments, the heater elements are placed in or proximate to themembrane 620, such as in the core, housing or support layer. Atemperature sensor (not shown) is placed within the core, to measure thetemperature of the fluid prior to its passage through the membrane. Acorresponding mated temperature sensor 630 is placed on the exterior ofthe filter, to measure the temperature of the fluid after it has passedthrough the membrane 620 and the co-located heating element. Asexplained above, the temperature difference observed by these twosensors allows the flow rate at that point to be measured. In theembodiment shown in FIG. 8, three flow rate sensors are shown, whereeach is adapted to measure the flow rate at a different section of thefilter element.

FIGS. 9 a-9 d show graphs illustrating exemplary flow rates observed bythe three sensors for a filter as it becomes clogged over its lifecycle. When a new filter is installed, all portions of the membrane areequally permeable. At this point in time, flow rates may be roughlyequal at all portions of the filter, as shown in FIG. 9 a.Alternatively, a higher flow rate may be seen at the leftmost sensor, asthis sensor is the one closest to the source, and fluid may exit throughthis sensor since it is the path of least resistance and shortestdistance. This is illustrated in FIG. 9 b. As the filtering element isused, splatter or foam from the material begins to coat the filter,typically beginning near the inlet of the filter. Thus, the flow rate asseen by the leftmost sensor is reduced, forcing an increase in flow atthe other locations, as shown in FIG. 9 c. As the filter continues toclog, the flow rate at the middle sensor also begins to decrease,forcing more of the flow through the rightmost part of the filter, asshown in FIG. 9 d.

Such a configuration is valuable in that absolute flow rate values areunnecessary. Rather, the relative values of the various sensors overtime are sufficient to understand the current permeability and conditionof the filter. For example, the actual flow rate values are not includedon FIGS. 9 a-9 d. However, the general shape of the graph, and therelationship between the flows at the various points allows one ofordinary skill in the art to understand the status of the membrane anddetermine whether replacement is required.

In other embodiment, a simple hot-wire anemometer can be used. In thisembodiment, a thin wire is placed in the flow of the fluid. This wire isthen energized by passing a current through it, thereby heating thewire. The fluid flow past the wire has the effect of removing heat as itis being generated by the wire, thereby cooling the wire. Thus, thegreater the fluid flow, the lower the temperature of the wire.Variations in the temperature of the wire cause similar variations inthe resistance of the wire. Thus, flow rate can be determined bymeasuring the resistance of the wire. In certain embodiments, known asconstant current anemometers (CCAs), a constant current is passedthrough the wire, and the voltage across the wire is measure todetermine its resistance. In other embodiments, known as constantvoltage anemometers (CVAs), a constant voltage is maintained across thewire, and the current is measured. In either scenario, the resistance ofthe wire can be determined, and consequently, the fluid flow can becalculated.

Thus, flow rate can be used to determine if a filter is becomingclogged. In other words, referring to FIG. 1, if the flow rate graduallydecreases, this may be an indication of wear out. Such an event wouldlead the CPU 340 to transition to the end of life mode 30.

While the flow rate sensor is useful in determining clogging within afilter, it can also be used to determine filter integrity. For example,if the flow rate as determined by one of the sensors undergoes asubstantial increase, an integrity issue may exist. A sudden increase inflow rate measured at one or more of the sensors may indicate that thefilter membrane has broken, thereby increasing the flow instantaneously.Thus, increases in flow rate can cause the CPU to transition to end oflife mode 30. Integrity issues can also be detected through the use ofpressure sensors. As is known to those of ordinary skill, thedifferential pressure between two points can be used to determine theflow rate of fluid passing between those points. These pressure sensorscan be connected to a processing unit such that the processor canmonitor the differential pressure across the thickness of the membranefor signs of integrity issues.

However, clogging is not the only concern. In certain situations, atemporary blockage may occur. In some environments, such as afermentation reactor, a material or byproduct of the reaction, such asthe protein foam, may accumulate on the top surface and be pushedupward. When it reaches the surface, the foam may burst as it contacts asurface and splash as the gas is released. At times, this material maysplash onto the filter element, causing it to clog. In some embodiments,this blockage is not permanent, and may be rectified by the applicationof sufficient heat so as to vaporize the splashed material. In such ascenario, the processing unit 340 may detect a sudden change in the flowthrough a particular portion of the filter. Based on this, theprocessing unit may regard this as an abrupt degradation in a measuredparameter, as shown in FIG. 1. The CPU 340 then moves to the recoverymode 20, where a corrective action will be attempted. In thisembodiment, the CPU 340 may apply a significant amount of current to theheating element, assuming that this change is due to a splash. Theprocessing unit will then continue to monitor the flow rate through thisportion of the filter. If the flow rate improves, then the assumptionwas correct, and the processing unit will return to the operating mode10.

However, if the flow rate does not improve to a specific value within apredetermined time period, the processing unit may determine that thefilter is sufficiently clogged such that heat alone cannot be used toremedy the situation. In such a scenario, the processing unit maytransition to the end of life mode 30, and notify an operator throughuse of an alert 380.

In an alternative embodiment, the abrupt degradation may be detectedusing a pressure sensor to detect a sudden increase in pressure withinthe container. This increase may correspond to a temporary blockage asdescribed above. Upon detecting such a pressure change, the stepsdescribed above can be executed to attempt to vaporize the material fromthe filter element. If the situation is not rectified, the processingunit may notify an operator through use of an alert.

In accordance with the embodiment shown in FIG. 5, the processor may bein communication with a number of different types of sensors. Aspreviously described, temperature sensors can be used to maintain apredetermined temperature for the filter element, and for calculatingflow rate. Pressure sensors can be used for flow rate or for integritytesting. Other types of sensors can also be employed. For example, in abioreactor, it may be known that a subcompound of the reaction has adeleterious effect on the hydrophobicity of filter membrane by changingthe surface energy. To counter this, the level of material within thebioreactor is kept sufficiently low so as not reach the vent filter.However, excessive foaming or splashing may cause material to reach thevent filter. A conductivity sensor, in conjunction with a processingunit, can be used to predict this condition and prepare for the pendingcontact.

EXAMPLE 2 Particulate Filter

In another embodiment, a filtration system for particulates, such ascell debris from a bioreactor or crystals from wine, may employ thetechnology described above.

A filtration system for particulates such as cell debris from abioreactor or crystals from wine is shown in FIG. 10. It consists ofhousing 702 containing one or more filters 704. The filter 704 isattached to the outlet 706 of the housing such that all filtratereaching the outlet 706 does so by having first passed through thefilter 704. The housing 702 also has an inlet 708 from a source of thefluid to be filtered. Downstream of the outlet 706 is a recirculationloop 710 which is connected via a first electronically actuated valve714, such as a solenoid valve, to the outlet 706 and to the side of thehousing 702 via a second electronically controlled valve 718. In thenormal closed position, filtrate leaving the outlet 706 is passeddownstream to the next location 718 such as a storage container or anadditional purification step. Inlet 708 also has an electronicallycontrolled valve 732 mounted adjacent the housing 702.

The filter 704 has a first sensor 720 mounted on the upstream side ofthe filter material and a second sensor 722 mounted downstream of thefilter material. Both sensors 720, 722 may contain a wirelesscommunication device such as a RFID tag. An additional computationallogic device such as a PID controller or CPU 724 is in communicationwith the two sensors 720, 722. This CPU 724 can compare and contrast thesignals from the two sensors 720, 722 against a known set of parameters.The processing unit 724 also is capable of controlling valves 714 and718 such as via a wireless communications device 726, 728, 734 containedin each of the valves 714, 718 and 732, respectively or via wiredcommunication. The wireless communication device may be any suitabletype, including but not limited to an RFID device, and a Zigbee device.The CPU 724 is able to actuate or deactuate the valves 714, 718, 732 asneeded. The sensors 720, 722 and the processing unit 724 may be poweredremotely such as by an inductive coupling device in the outlet of thehousing 702. The wireless communications devices 726, 728, 734 of thevalves 714, 718 and 732 and the valves themselves 714, 718 and 732 maybe powered by a hard wire electric connection to the system power supply(not shown).

Unfiltered wine containing crystals to be removed is passed from theinlet 708 into the housing 702 and through the filter (such as aPolySep® II filter available from Millipore Corporation) to the outlet706 of the system. The first and second sensors 720, 722 are monitoredby the processing unit 724 at an interval, such as every 2 minutes. Inthis embodiment, no maintenance action is required to retain the filterin operating mode 10.

However, when the pressure value between the two sensors 720, 722 isfound to differ by more than a predetermined amount, such as two (2)psig, the processing unit7824 initiates a corrective action. Theprocessing unit 724 sends a signal to cause the valves 712 and 718 toopen and valve 732 to close. In this embodiment, the actuators shown inFIG. 2 are actually outside of the filter element, however they arecontrolled by the processing unit within the filter element. However,another embodiment collocates the actuators and valves within the filterhousing thereby improving the response time and sensitivity of themeasurements and corrective actions.

This corrective action diverts the filtrate from the outlet 706 backinto the housing 702 via the recirculation loop 710 at a point adjacentto the outside of the filter 704 where valve 718 is located. This causesany sediment built up to be dislodged from the outer surfaces of thefilter 704. This flushing may occur for a fixed amount of time, such as30 seconds. After the predetermined time period has elapsed, theprocessing unit 724 then commands valves 712 and 718 to close and valve732 to open. Valve 744 is then opened to drain the loop 710. Processingunit 724 then compares and contrasts the signals from the two sensors720, 722 against a known set of parameters upon reactivation of thesystem to its forward flow/filtration sequence.

In the event that the flushing does not improve the filtration (viamaintaining the pressure differential within the prescribeddifferential), the processing unit 724 may try the corrective action(e.g. flushing) a second time and again measure and compare the pressuredifferential against the set standard.

If the difference still does not fall within the prescribed range, theprocessing unit then moves to end of life mode 30, where an alarm (notshown) is set off, indicating to the operator that the filter needs tobe replaced.

If the flushing restores the differential pressure to an acceptablevalue, the processing unit 724 returns to operating mode 10, where itsimply continues to monitor the differential pressure between sensors720, 722.

In a different embodiment of this example, the pressure sensors 720, 722are replaced by flow rate sensors. The processing unit 724 now monitorsthe flow rate through the filter in order to make its determinationsabout mode changes and corrective actions. With this exception, thesystem functions equivalent to that described above. In yet anotherembodiment, a single flow rate sensor is placed on the downstream sideof the filter, and is monitored by the processing unit 724. Rather thanmeasure differential flow rates, the processing unit 724 simply monitorsabsolute flow rate through the filter.

EXAMPLE 3 TFF Filters

Tangential Flow Filters (TFF) are commonly used to separate proteinsfrom a filtrate. Since the proteins may clog the membrane, the fluidflows past the membrane in a tangential direction. FIG. 11 a shows theflow of a traditional filter, wherein the fluid flows toward, or normalto, the surface of the membrane. FIG. 11 b illustrates the operation ofa TFF filter, where the fluid flow is tangential to the surface of themembrane. This allows few particles to gather on the membrane, therebyreducing the incidence of clogging.

FIG. 12 shows a traditional concentration TFF system. Fluid from a feedtank 800 is pumped in a circuitous path into a TFF filter 810 and backto the feed tank 800. The TFF filter 810 filters filtrate from thefluid, which exits the system via filtrate stream 820. As this processcontinues, the concentration of retentate increases. During each pass offluid over the surface of the filter membrane, the applied pressureforces a portion of the fluid through the membrane and into the filtratestream 920. The result is a gradient in the feedstock concentration fromthe bulk conditions at the center of the channel to the moreconcentrated wall conditions at the membrane surface. There is also aconcentration gradient along the length of the feed channel from theinlet to the outlet (retentate) as progressively more fluid passes tothe filtrate side.

FIG. 14 illustrates the flows and forces described above with theparameters defined as:

Q_(F): feed flow rate [L/h]

Q_(R): retentate flow rate [L/h]

Q_(f): filtrate flow rate [L/h]

C_(b): component concentration in the bulk solution [g/L]

C_(W): component concentration at membrane surface [g/L]

C_(f): component concentration in filtrate stream [g/L]

TMP: applied pressure across the membrane [bar]

Transmembrane pressure (TMP) is defined as the pressure differentialacross the TFF membrane. Referring to FIG. 12, it is the averagepressure on the fluid side, typically defined as the average of the feedpressure 830 and the retentate pressure 840, less the pressure on thefiltrate side.

It is known that maintaining a TMP within a certain range improves theoperation and performance of the TFF filter. Often, very high wallconcentrations and high membrane fouling occur, especially during thestartup of the process. To reduce the filtrate rate and enable the TMPto be controlled at the low values required for robust TFF operationsthe filtrate flow must be controlled.

In a controlled flow filtrate operation, a pump or valve 860 on thefiltrate line restricts filtrate flow to a set value, as shown in FIG.13. In addition to reducing the filtrate flow to maintain adequatetangential flow, it creates pressure in the filtrate line to reduce theTMP while the feed and retentate pressures remain fixed.

By monitoring the feed pressure and the retentate pressure, it ispossible to determine the optimal pressure on the filtrate side of thefilter. The filtrate pump or valve 860 is then adjusted to achieve thispressure.

Having defined the typical operation of a TFF filter, the use of anautonomous TFF filter will now be described.

As shown in FIG. 15, the filter 900 has a first sensor 920 mounted onthe upstream side of the filter membrane and a second sensor 922 mounteddownstream of the filter membrane. Both sensors may be proximate to therelative side of the filter and do not necessarily have to be andpreferably are not in contact with the membrane itself, so as to obscurethe filtration function. For example they may be located in the feed andfiltrate channels adjacent the respective side of the filter. They mayalso be mounted on an inner wall of either channel and the like. Bothsensors 920, 922 may contain a wireless communication device such as aRFID tag. An additional computational logic device such as a PIDcontroller or CPU 924 is in communication with the two sensors 920, 922.This CPU 924 can compare and contrast the signals from the two sensors920, 922 against a known set of parameters. The processing unit 924 alsois capable of controlling valves or pump 914 such as via a wirelesscommunications device 926 contained in valve or pump 914 or via wiredcommunication. The wireless communication device may be any suitabletype, including but not limited to an RFID device, Bluetooth device anda Zigbee device. The CPU 924 is able to actuate or deactuate the valveor pump 924 as needed. The sensors 920, 922 and the processing unit 924may be powered remotely such as by an inductive coupling device in theoutlet of the housing. The wireless communications devices 926 of thevalve or pump 1014 and the valve or pump itself 914 may be powered by ahard wire electric connection to the system power supply (not shown).

As explained above, fluid is passed tangentially over the filtermembrane. Filtrate passes through the membrane and becomes part of thefiltrate stream. In some embodiments, there is no maintenance action 12required by the TFF filter. However, in other embodiments, theprocessing unit in the TFF filter may continuously monitor the upstreamand downstream pressure, via sensors 920, 922. Based on the differencebetween these values, the processing unit may control the valve or pump914, thereby indirectly controlling the downstream pressure and the TMP.

At some point, the upstream pressure, or the TMP, may reach a levelwhich cannot be rectified by adjusting the valve or pump 914. In thiscase, the filer may move to recovery mode 20, where a corrective actionis performed. In one embodiment, the filter has one or more piezoelectric devices, which vibrate when energized, located on or near thefilter membrane. In this embodiment, the controller 924 actuates thepiezo electric devices 930. These piezo electric devices are located onthe filter element, preferably close or affixed to the membrane. Whenactuated, these devices 930 vibrate in response to electrical current.The resulting vibration causes the particulate that has accumulated onthe membrane to break free and move in the tangential flow, therebylowering the upstream pressure. Although piezo electric devices causethe desired vibration thereby loosening the accumulated material, othermechanical or electrical embodiments may be used. For instance, asproteins are known to be electrically polar as used in GelElectrophoresis, a temporary electrical voltage potential could be usedto temporarily draw off proteins from the membrane surface.

If this occurs, then the processing unit 924 returns to the normaloperating mode 10. However, if the vibration or other method isunsuccessful in removing the particulate, the processing unit mayattempt the recovery action one or more times. If after thepredetermined number of attempts, the action is unable to remove theparticulate, the processor 924 may move to the end of life mode 30. Inthis mode, the processing unit alerts the operator, as described above.

In an alternative arrangement, one might use a backflush of fluidthrough the membrane from the filtrate side to the feed side to dislodgethe accumulated particulate from the feed side surface of the membrane.The filtrate pump 860 can be reversed and draw filtrate back through themembrane. Feed pump 850 may either be shut off or reduced in speed ifdesired or required to achieve the backflush. The backflushed filtratethen flows back through the retentate line to the feed tank. As anotheralternative, buffer solution could be fed from the filtrate side throughthe membrane to backflush it so that filtrate is not required to befiltered twice.

If this occurs, then the processing unit 924 returns to the normaloperating mode 10. However, if the backflush is unsuccessful in removingthe particulate, the processing unit may attempt the recovery action oneor more times. If after the predetermined number of attempts, the actionis unable to remove the particulate, the processor 924 may move to theend of life mode 30. In this mode, the processing unit alerts theoperator, as described above.

In each of these situations, the present invention detects the issue andalerts the operator of the problem. This alert mechanism can be ofvarious types. In some embodiments, a sensory alert, such as visual orauditory, is utilized. In these cases, a LED may illuminate or a devicemay sound to indicate a condition that must be attended to by theoperator. In other embodiments, information concerning the error istransmitted wirelessly to a remote device, which receives the wirelesstransmission, and subsequently alerts the operator, such as through agraphic message on a video display unit.

The filter of the present invention is adapted to maintain the operatingconditions of the filtering element, recover from temporary errorconditions, and report uncorrectable errors to an operator.

The processing unit can also detect sudden changes in flow rate and/orpressure, which may indicate a transient error, such as materialsplashing. Based on this assumption, the processing unit can employrecovery techniques, such as elevated temperatures, to attempt tocorrect the problem.

Finally, in the event of a clogged filter, which cannot be rectified bythe processing unit, an alert can be sent to an operator, signifyingthat the filtering element requires servicing.

The above examples show several embodiments of the present invention. Inall embodiments, the filter element comprises a processing unit, capableof operating in three different modes, and at least one sensor. Thissensor may be a pressure sensor, temperature sensor, flow sensor, a pHsensor, or any other suitable type. In addition, the processing unit hasthe ability to control at least one actuator, which is used duringrecovery mode. In some embodiments, the processing unit also controls atleast one actuator during the maintenance action in normal mode. Itshould be noted that in some cases, such as Example 1, the processingunit, sensors and actuators are all contained within the filter. Inother embodiments, such as Example 2, the actuators are located separatefrom the filter, but are controlled by the processing unit in thefilter. Finally, in Example 3, one actuator is located on the filter,while a second actuator is located separate from the filter.

The terms and expressions which have been employed herein are used asterms of description and not of limitation, and there is no intention inthe use of such terms and expressions of excluding any equivalents ofthe features shown and described (or portions thereof). It is alsorecognized that various modifications are possible within the scope ofthe claims. Other modifications, variations, and alternatives are alsopossible. Accordingly, the foregoing description is by way of exampleonly and is not intended as limiting.

1. An autonomous filtering device, comprising: a. A filter elementhaving a membrane through which said fluids can pass and a housing tosupport said membrane; and b. At least one sensor located within saidfilter element adapted to monitor at least one parameter associated withsaid filtering device; c. A mechanism to indicate an alert to anoperator; and d. A processing unit in communication with said sensor andsaid mechanism, and adapted to control an actuator, wherein saidprocessing unit is adapted to operate in each of three modes, wherein afirst mode is used during normal operation, a second mode is used tocontrol said actuator, and a third mode is used to activate said alertmechanism.
 2. The element of claim 1, wherein said actuator is selectedfrom the group consisting of a piezo electric device, an electromotiveforce device, a heating element, a valve, and a pump.
 3. The element ofclaim 1, wherein said processing unit transitions between said modebased on the output of said sensor.
 4. The element of claim 3, whereinsaid processing unit transitions from said first mode to said secondmode if said sensor output is outside an acceptable range.
 5. Theelement of claim 4, wherein said processing element controls saidactuator, said actuator adapted to affect said parameter monitored bysaid sensor.
 6. The element of claim 5, wherein said processing unittransitions from said second mode to said first mode, if said sensoroutput reverts to an acceptable range.
 7. The element of claim 5,wherein said processing unit transitions from said second mode to saidthird mode is said sensor output does not return to an acceptable range.